Indian Journal of Clinical and Experimental Ophthalmology

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Indian Journal of Clinical and Experimental Ophthalmology (IJCEO) is open access, a peer-reviewed medical journal, published quarterly, online, and in print, by the Innovative Education and Scientific Research Foundation (IESRF) since 2015. To fulfil our aim of rapid dissemination of knowledge, we publish articles ‘Ahead of Print’ on acceptance. In addition, the journal allows free access (Open Access) to its content, which is likely to attract more readers and citations of articles published in IJCEO. Manuscripts must be prepared in more...

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Get Permission Mathukumalli, Tumma, and Mukkamala: A study on central corneal thickness in diabetics and non – diabetics


Introduction

Diabetes mellitus (DM) is one of the widely spreading non – communicable diseases. It is one of the most leading causes of blindness with complications related to diabetic keratopathy (DK) and diabetic retinopathy (DR). Main indications of DM related to ocular system are retinopathy, cataract, glaucoma. Changes related to cornea are diabetic keratopathy. Corneal pathologies like superficial punctate keratitis, corneal sensitivity seen in diabetic patients.

Corneal in an avascular structure, and it is made up of five layers. Outermost layer is epithelium then bowman’s membrane and the stroma inner to it, Descemet’s membrane is fourth layer and inner layer is endothelium. Within the stroma collagen fibers are arranged parallelly in one plane and in consecutive plane fibers are arranged perpendicularly, since fibers are arranged regularly transparency of the cornea is maintained.

Since cornea is an avascular structure, it will get its nutrients from the aqueous humor which is produced by the ciliary body. Aqueous humor has all the nutrients required for metabolism and maintenance of cornea. Glucose in the aqueous humor affects the metabolic status of the cornea. Endothelial cells of cornea have Na+ - K+ ATPases that are actively pumping out water from the stroma and maintain the stromal integrity and structure. Endothelial cells are monolayer cells present inside the Descemet’s membrane. These cells do not have ability to regenerate if the cells are degenerated because of any pathology. These cells are hexagonal in its shape.

In diabetics blood glucose levels are high, such high glucose levels are present in the aqueous humor also. This glucose molecules are taken up by the stroma for its metabolism, water follows glucose to maintain osmolarity. This leads to corneal edema which is one of the complications of the diabetes and structural integrity of the cornea is altered. Since cornea is edematous its thickness increases. In chronic metabolic stress where blood glucose levels are high advanced glycosylated end products (AGE’s) are formed, those products enter into the stroma of the cornea and binds to the collagen fibers. These products make cross linking between the fibers leads to changes in the corneal thickness.

This chronic metabolic stress makes changes in the endothelial cells of the cornea by loss in hexagonality, pleomorphism, corneal autofluorescence, degeneration of the cells due to stress leads to over hydration of the stroma leads to change in corneal thickness. DM also decreases the activity of Na+ - K+ ATPase whose activity is regulated by the insulin. Therefore, insulin resistant diabetics are more prone to develop more complicated corneal changes compare to insulin dependent diabetics. Since the activity of the Na+ - K+ ATPases is altered corneal over hydration takes place and thickness of the cornea changes. All the parameters finally lead to the changes in the corneal power and visual acuity will be decreased.

The central corneal thickness is a sensitive indicator of corneal health and serves as an index for corneal hydration and metabolism. It is also an important indicator of patency of corneal endothelium pump and can be objectively measured by variety of techniques. With the advent of precise and better non-invasive measurement tools, central corneal thickness (CCT) measurement has become a vital ocular parameter due to its importance as an indicator of corneal health and integrity. Accurate CCT measurement has diagnostic and therapeutic implications in various conditions like corneal dystrophies (Keratoconus, Pellucid marginal degeneration), contact lens related problems, dry eyes, diabetes mellitus, glaucoma and refractive surgery.

In this cross-sectional comparative study with the basis of HbA1c levels of the diabetic patients of age group 45 to 80 years and age matched controls are taken into consideration for the study.

Aim and Objective

To determine the change in thickness of cornea in diabetics and non-diabetics using Optical Coherence Tomography (OCT).

Materials and Methods

In this cross-sectional comparative study, a total number of patients 260 were included in this study. Patients were divided into two groups using random sampling. Group 1 included patients with diabetes and group II patients without diabetes (Control group) of age group between 45 to 80 years who are attending Ophthalmology OPD department were considered.

All the diabetic and age matched patients attended to Ophthalmology OPD were included in the study after explaining procedure and taking informed consent. Thorough history of patients was taken. All the patients underwent visual acuity testing, BCVA, intraocular pressure measurement, fundus examination, HbA1c and Optical Coherence Tomography (OCT).

Ethical committee approval was obtained from institutional ethics committee.

Inclusion criteria

  1.  Patients with age group 45-80 years was considered.

  2.  Patients who are willing to give informed consent was considered.

Exclusion criteria

Patients with history of Intraocular surgeries, Trauma, Retinal lasers, corneal opacities and dystrophies, glaucoma, pseudo-exfoliation, uveitis, usage contact lenses and Use of topical eye drops were excluded

Statistical analysis

Data was analyzed using IBM SPSS software version 26 (trail version).

Sample size was derived by using 95% of confidence interval Different parameters were compared using Chi-square test, independent samples t-test and Z -test. P value of <0.05 was considered significant.

Results

Table 1

Demographic and clinical profile of clinical population

Parameter

Diabetic (n=130)

Non-Diabetic (n=130)

p Value

Gender

Male

58 (44.615%)

55 (42.307%)

0.7

Female

72 (55.385%)

75 (57.693%)

0.7

Duration of DM

< 10 years

112(86.154%)

-

≥ 10 years

18 (13.846%)

-

HbA1c (%) ≤ 7.5

63 (48.462%)

130 (100%)

<0.0001

> 7.5

67 (51.538%)

0

Table 2

Parameter

Diabetic (130)

Non – Diabetic (130)

p value

Age years)

62.95±9.47

62.66±9.56

0.810

HbA1c %)

7.86±1.44

5.40±0.75

<0.001

CCT (µm) mean ± SD

560.38±44.51

500.32±39.63

<0.001

Table 3

Difference of two means

Parameters

Age (years)

CCT (µm)

Duration(years)

<10 years

62.77±9.54

526.85±50.07

≥10 years

63.39±9.22

577.39±51.81

p value

0.789

<0.001

HbA1c (%)

≤7.5

63.06±9.57

517±48.04

>7.5

62.09±9.33

568.66±42.14

p value

0.4715

<0.001

Difference of two means

Data of 260 (130 diabetic patients and 130 non-diabetic patients) eyes was evaluated. Mean age of diabetic population was 62.95±9.47 years, while mean age of control group was 62.66±9.56 years. Mean HbA1c in diabetic population was 7.86±1.44%, while in control group was 5.40±0.75% with statistically significant p value of < 0.001.

Mean CCT in diabetic population was 560.38±44.51 µm, while in control group was 500.32±39.63 µm with statistically significant p value of < 0.001. Mean CCT with duration of diabetes in <10 years age group was 526.85±50.07 µm, while in control group was 577.39±51.81 µm with statistically significant p value of < 0.001. Mean CCT with HbA1c levels of ≤ 7.5% was 517±48.04 µm, while in control group was 568.66±42.14 µm with statistically significant p value of <0.001. Duration of diabetes and is significantly correlated with CCT. HbA1c levels also significantly correlated with CCT. Correlation analysis showed that duration of diabetes and HbA1c shows significant correlation with CCT. However, age did not show any significant correlation with CCT.

Discussion

The majority of studies, including the current study, revealed that diabetic eyes exhibited higher CCT than non-diabetic eyes.1, 2, 3, 4, 5

Why does the corneal thickness in diabetic eyes increase? It is hypothesised that an increase in stromal hydration is caused by an endothelial pump function disfunction brought on by a decrease in Na+/K+ ATPase activity, despite the fact that the reason is unknown.4, 5, 6

What impact does glycaemic control have on CCT? Recently, emphasis has been placed on HbA1c level as a crucial indicator of glycaemic management. A protein contained in RBC is called haemoglobin. A1c is created in the bloodstream when glucose binds to the red pigment of haemoglobin (HbA1c). Red blood cells have a lifespan of 8 to 12 weeks.

One may anticipate that hyperglycaemia would also have an impact on corneal moisture and result in both qualitative and quantitative alterations to the cornea, including adjustments to its refractive index, curvature of the cornea, and corneal thickness.7, 8 In our study, a higher HbA1c, a measure of poor glycaemic management, was linked to thicker corneas.

Additionally, one may anticipate that disease duration and severity would both have an impact on corneal thickness. However, there was no way to tell if these characteristics ha any impact on corneal thickness. This may be a result of several homeostatic modifications that diabetics experience during the course of their chronic condition. Therefore, in order to determine the precise association between blood glucose and the cornea, longitudinal follow-up investigations must be carried out.

Therefore, more glucose in the blood at this period, more it will adhere to the haemoglobin. Blood HbA1c readings give insight into the past two to three months' typical blood glucose levels. As a result, routine HbA1c testing monitors recent glycemic management. We looked into HbA1c numbers and how they related to CCT. Patients who had greater HbA1c levels (7%) had increased CCT than those who had lower HbA1c levels (7%).1

Larsson et al.3 and Keoleian et al.9 found no association between HbA1c and CCT. Keoleian et al. found that despite the anatomical abnormalities of the corneal endothelium in diabetes patients, the endothelium's functional state was unaltered. They stated that there was no discernible change in the corneal thickness of diabetics.

In a related study, Claramonte et al.10 found a strong correlation between diabetes mellitus and CCT. In their study, diabetics' mean CCT was 571.96, compared to non-diabetics' 544.89, with a statistically significant difference.

In a study by Mehmet Özgür ZENGİN et al1 they found correlation between HbA1C and CCT.

In another study by Kumari et al., the mean CCT was likewise greater in people with diabetes who had it for more than 10 years (544.6434.56) than it was in those who had it for shorter than 10 years (518.9831.21).11

McNamara et al 12 discovered no direct link between HbA1c level and CCT in type 2 diabetes but identified a favourable correlation between HbA1c level and CCT in type 1 diabetics who also had thicker corneas.7

Table 4

Study

Cohort

Results

Srećković S, et al. (2022)13

49- type 2 Diabetics 47- non diabetic control group

CCT was not statistically significantly impacted by the presence of retinopathy.

Yoo Jin Kim & TaeGi Kim (2021)14

511 (1022 eyes) type 2 diabetes patients 900 (1799 eyes) non-diabetic patients.

Age-related diabetes and chronic diabetes with greater HbA1c have an impact on ocular endothelial cells.

C V Reddy,*, and M H Reddy15

168 subjects divided into 3 groups: 40 diabetics duration >10 yrs, 46 diabetics duration ≤10 yrs, 82 controls.

Compared to people without diabetes, those who have type 2 diabetes mellitus have corneas that are thicker.

Handan Canan*, et al,16

47 patients in Group I with diabetic retinopathy changes and 49 patients in Group II without diabetic retinopathy changes

The CCT was not much impacted by the duration of DM or the existence of diabetic retinopathy.

Rajni Sethia et al17

150 type-II DM patients were conducted (only left eye included)

DM duration, HbA1c levels, and corneal thickness are unaffected

Qamar-ul-Islam et al18

252 eyes 126 diabetic patients 126 healthy controls

In comparison to age-matched healthy controls, patients with DM had significantly thicker CCT.

Kumari et al11

The corneal thickness assessment was done for 100 eyes of 50 diabetic and 100 eyes of 50 non diabetic patients

Patients with diabetes have thicker corneas than people without diabetes. Diabetes and CCT are related in a direct manner.

Mehmet Ozgür ZENGİN et al1

136 type II diabetic patients and 36 non-diabetic healthy subjects

Contrary to healthy individuals, type II diabetic patients have thicker corneas.

Lee et al.2

200 insulin dependent diabetics and 100 controls

CCT and disease duration were associated

Keoleian et al.9

14 type I diabetics, 14 control subjects

CCT [560 m] compared favourably to controls [560 m].

Larsson et al3

49 type 1 diabetics, 60 type 2 diabetics, 62 control subjects

CCT was similar in diabetics with type I (580 m) and type II (570 m) diabetes.

Roszkowska et al.5

30 type I diabetics 45 type 2 diabetics 62 controls

When compared to controls, CCT was greater in both type I (580 m) and type II (570 m) diabetics (540 m for type I controls). For class II controls, 550 m

In our study duration of diabetes data is as follows ‹10 years 112(86.154%) and ≥ 10 years 18 (13.846%). In our study the mean CCT in diabetics was 560.38±44.51 and in non-diabetics was 500.32±39.63 and the difference between the two groups was statistically significant (p value 0.001).

In our study, the mean CCT value in diabetics < 10 years duration was 526.85±50.07 and in diabetics >10 years of duration it was 577.39±51.81. This shows a correlation between duration and diabetes and CCT with significant p value <0.001).

Mean of HbA1C levels of ≤7.5 was 517±48.04 when compared to patients with HbA1C levels of >7.5 was 568.66±42.14. In our study a correlation between HbA1C levels and CCT was noted with a statistically significance (p value <0.001).

Limitations of this Study

Confocal microscopy which is more appropriate method of evaluating changes in corneal thickness was not used. Many other systemic diseases which effect central corneal thickness like Hypertension hyperlipidemia were not considered.

Conclusion

Our study demonstrates that individuals with diabetes mellitus or higher levels of glycosylated haemoglobin had higher CCT, regardless of age or gender. These findings imply that chronic hyperglycemia may influence CCT measures, and they, along with results from subsequent studies, may contribute to our understanding of the pathophysiological mechanisms behind diabetes. Increased CCT and diabetes were shown to be significantly correlated, and thick corneas were positively correlated with the length of diabetes, suggesting that people with thick corneas are more likely to have the disease at an advanced stage.

The correct assessment of these patients with regard to their functional result can be made more reliable by the measurement of CCT in conjunction with research on the corneal endothelium. The creation of covalent bonds in the corneal stroma is the primary histological change, hence research into the relationship between diabetic keratopathy and corneal ectatic state is necessary.

Source of Funding

None.

Conflict of Interest

None.

References

1 

MÖ Zengin Z Özbek G Arikan İ Durak AO Saatci Does central corneal thickness correlate with haemoglobin A1c level and disease severity in diabetes type II?Turk J Med Sci201040567580

2 

JS Lee BS Oum HY Choi JE Lee BM Cho Differences in corneal thickness and corneal endothelium related to duration in diabetesEye2006203158

3 

LI Larsson WM Bourne JM Pach RF Brubaker Structure and function of the corneal endothelium in diabetes mellitus type I and type IIArch Ophthalmol1996114914

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N Busted T Olsen O Schmitz Clinical observations on the corneal thickness and the corneal endothelium in diabetes mellitusBr J Ophthalmol1981651068790

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AM Roszkowska CG Tringali P Colosi CA Squeri G Ferreri Corneal endothelium evaluation in type I and type II diabetes mellitusOphthalmologica1999213425861

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PR Herse Corneal hydration control in normal and alloxan induced diabetic rabbitsInvest Ophthalmol Vis Sci19903111220513

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Y Saito G Ohmi S Kinoshita Y Nakamura K Ogawa S Harino Transient hyperopia with lens swelling at initial therapy in diabetesBr J Ophthalmol19937731458

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JB Dickey MJ Daily Transient posterior subcapsular lens opacities in diabetes mellitusAm J Ophthalmol199311522348

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GM Keoleian JM Pach DO Hodge SD Trocme WM Bourne Structural and functional studies of the corneal endothelium in diabetes mellitusAm J Ophthalmol199211316470

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P Claramonte JM Ruiz-Moreno SI Sánchez-Pérez M León C Griñó VD Cerviño Variation of central corneal thickness in diabetic patients as detected by ultrasonic pachymetryArch Soc Esp Oftalmol20068195236

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R Kumari BC Saha Central Corneal Thickness and Diabetes - A Study of Correlation in terms of Duration and Glycemic ControlInt J Contemp Med Res2015437679

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NA Mcnamara RJ Brand KA Polse WM Bourne Corneal function during normal and high serum glucose levels in diabetesInvest Ophthalmol Vis Sci1998391317

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S Srećković T Dušan R Danijela P Nenad S Jasmina ŠV Tatjana The influence of diabetes mellitus type 2 on the central corneal thicknessVojnosanit Pregl202279323842

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YJ Kim TG Kim The effects of type 2 diabetes mellitus on the corneal endothelium and central corneal thicknessSci Rep20211118324

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R Sethia A Patel H Shah R Patel T Rajput A study of correlation between HbA1c level & corneal thickness in diabetes mellitus patientsIndian J Clin Exp Ophthalmol201841969

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H Canan N Sahinoglu-Keskek RA Yaycioglu The relationship of central corneal thickness with the status of diabetic retinopathyBMC Ophthalmol2020201220

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CV Reddy MH Reddy A comparative study of central corneal thickness in diabetics and non-diabetics using ultrasonic pachymetryIndian J Clin Exp Ophthalmol20217355461

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Q Ul-Islam Effect of diabetes mellitus on central corneal thickness- A comparative studyPak J Ophthalmol201733312631



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Article type

Original Article


Article page

363-367


Authors Details

Sumalath Sai Keerthi Mathukumalli*, Bharath Tumma, Narasimha Mukkamala


Article History

Received : 10-11-2023

Accepted : 11-12-2023


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